Page 112 - Glucose Monitoring Devices

Glucose transduction technologies 113

Current technologies
Transduction technologies used in commercially approved CGMs
Enzymatic, electrochemical-based sensors
The transduction technologies used in most commercial CGM systems (as well as
most home blood glucose meters) rely on the measurement of an electrochemical
signal generated from the reaction of an enzyme, glucose oxidase (GOx), with
glucose [7,37]. Glucose oxidase-based sensing offers excellent selectivity for
glucose over other compounds that are endogenous to biological fluids and is a
well-established technology that has been in use for several decades. The first of
such glucose sensors was developed in 1962 by Clark and Lyons from the Children’s
Hospital of Cincinnati. Their glucose sensor was composed of an oxygen electrode,
an inner oxygen semipermeable membrane, a thin layer of GOx, and an outer dial-
ysis membrane. Glucose concentrations were determined by measuring the decrease
in oxygen concentration [43].
Two different approaches, referred to in the literature as “generations” of glucose
oxidase sensors [7,37,44], are used in commercial CGM systems. In the first
approach [4], glucose oxidase catalyzes the conversion of glucose and oxygen
(O 2 ) to gluconic acid and hydrogen peroxide (H 2 O 2 ). The net reaction can be shown
as follows:

Glucose þ O 2 / Gluconic Acid þ H 2 O 2
Glucose concentration can be determined by monitoring either the consumption
of O 2 or the generation of H 2 O 2 . A concentration-dependent current can be
measured electrochemically via oxidation or reduction of those species at an elec-
trode [39,65]. Systems from Dexcom (San Diego, CA) and Medtronic (Northridge,
CA) measure the oxidation of hydrogen peroxide at the surface of a working
electrode [49]. This approach requires the oxygen concentration to be in excess rela-
tive to the glucose concentration such that the reaction is glucose concentration
limited [49]. As oxygen concentrations in the interstitial space fluid (ISF) are
substantially less than glucose concentrations, the addition of glucose limiting mem-
branes as components of the sensors is required to correct the oxygen-to-glucose
imbalance and reduce or eliminate the oxygen dependency [49].
A second approach (i.e., generation) developed by Heller and colleagues [50]
and used by Abbott Diabetes Care (Alameda, CA) employs a synthetic, polymeric
redox-active mediator (Med) in place of oxygen, thus removing the dependency
on sufficient oxygen concentration in the ISF and also the potential for local tissue
irritation and sensor degradation that may arise from the overproduction of hydrogen
peroxide. This reaction can be shown as follows:
Glucose þ Med / Gluconic Acid þ Med (red)
The polymeric mediator is covalently attached to the GOx such that it connects
the enzyme reaction center to the surface of the electrode. The electrochemical
oxidation of the reduced (Med red ) redox-active polymer (which regenerates the